University of Utah researchers develop genetic map for Down syndrome diseases

The X might not be clearly marked, but researchers at the University of Utah have developed a high-resolution genetic map that outlines the development of diseases often associated with Down syndrome.

The X might not be clearly marked, but researchers at the University of Utah have developed a high-resolution genetic map that outlines the development of diseases often associated with Down syndrome.

Down syndrome individuals typically face a host of problems such as intellectual disabilities, heart defects and Alzheimer's disease. The map, produced by researchers at the U. Brain Institute and colleagues at Yale University, may help direct future studies and clinical treatments for a wide range of birth defects related to the disability.

"In particular, our map focuses in on an essential role for several genes," said Julie Korenberg, professor of pediatric genetics at the U. and lead researcher on the study. "These findings powerfully point the way to the mechanisms underlying birth defects, heart disease and leukemia — the critical knowledge for drug discovery and new treatments."

Korenberg led a team of researchers that worked with a grouping of 31 rare individuals with Down syndrome who hosted only partial duplications of chromosome 21.

Typically, those with Down syndrome have a complete extra copy of the chromosome. Korenberg said those who were studied provided critical human models for examining the features of Down syndrome in normal populations.

"The function of most of the genes in the genome are unknown," Korenberg said. "What this study does is relates, using these rare cases, to start and put together how genes and the genome build development."

The understanding of genetic origins that are illustrated by the map may eventually unlock the causes of congenital heart disease, an ailment that is the most common cause of hospital stays in children, according to a release from the Brain Institute. In addition, the map allows future researchers to focus more keenly on critical regions of the human genome.

The map was developed using microarray methods, which can identify duplicated regions down to single segments of DNA or RNA. The teams of Korenberg and Michael Snyder of Yale used those methods to map the breakpoints in the genes of their subjects to develop their findings, according to the release.

"This is the highest resolution Down syndrome phenotype map to date and it lets us identify distinct genomic regions that likely contribute to the manifestation of eight Down syndrome features," said Korenberg, who has dedicated more than 20 years to identifying sections of chromosomes that are involved in birth defects of Down syndrome.

The features or regions of critical genes that teams have identified include acute megakaryocytic leukemia, Hirchsprung disease and severe mental retardation.

Korenberg and Snyder published their findings in Tuesday's issue of Proceedings of the National Academy of Sciences.